1. Field of the Invention
This invention pertains to pharmaceutical manufacturing and particularly to determining the formulation orientation of multi-layer capsule shaped tablets with respect to different internal formulation layers proximate to the opposite narrow and rounded ends of the tablets. In particular, the present invention pertains to rapidly and accurately determining the formulation orientation of such tablets by including a specific color scheme in the multi-layer design of the tablets that permits color detection at a spot location on the side of the tablet to be used for determining the formulation orientation.
2. Description of the Related Art Including Information Disclosed Under 37 CFR 1.97 and 1.98
Colorants may be used as an indicator of different formulation layers in multi-layer dosage forms. Formulating different formulation layers with different colorants is a useful quality control method that helps ensure that the different formulation layers are distinguishable from each other during the manufacturing process. Different colors included in the different layers can be used to determine the formulation orientation of the dosage form with respect to the internal formulation layers when such a determination is required for a particular processing step. An example of such a processing step is drilling of a delivery port in a multi-layer osmotic dosage form. These dosage forms have an internal compartment containing at least one drug containing layer, at least one expandable polymer-containing layer and, optionally, one or more drug-free layers to produce a desired release pattern such as delayed or pulse release. The internal compartment is surrounded by a membrane that is at least partially semipermeable and at least one delivery port is formed through the membrane at an appropriate location to permit release of drug-containing formulation from within the compartment. The expandable polymer-containing layer is known as a “push” layer 10 because, following oral administration, fluid is imbibed through the semipermeable membrane causing the drug-containing layer(s) and any optional drug-free layer(s) to form a dispensable formulation and causing the polymer layer to expand and “push” the dispensable formulation through the delivery port.
Such osmotic dosage forms are typically manufactured by compressing the component dispensable formulation-forming layer(s) and the push layer(s) together to form a multi-layer internal core, applying the semipermeable membrane around the core and then drilling, typically with a laser, an appropriate delivery port. It will be appreciated that these dosage forms are internally non-symmetrical in that one or more portions contain the dispensable formulation-forming layer(s) and one or more portions contain the push layer(s). Generally, the push layer is adjacent to one end, the “push end,” of the tablet and the opposite end is the “dispensing end” that is proximal to the dispensable formulation-forming layer(s) within the dosage form. Proper operation of the dosage form requires that the delivery port be formed in the dispensing end of the dosage form and not in the push end of the dosage form. Thus, at some point prior to the laser drilling step, the internal formulation orientation of the dosage forms with respect to these opposite ends must be determined to ensure that the delivery port is drilled in the dispensing end, and not the push end, of each tablet.
Typically, multi-layer osmotic tablets have been produced in conventional tablet shapes such that a broad front surface encompasses the dispensing end of the tablet and the opposite broad back surface encompasses the push end of the tablet. By including a colorant in at least one formulation layer proximate to either the dispensing end or the push end of the tablet, a contrast or color detector can be used to determine the formulation orientation of the tablets with respect to the front and back surfaces. Useful methods and apparatus for determining the formulation orientation of such tablets and for drilling the delivery ports in the dispensing ends of the tablets are disclosed and claimed in U.S. Pat. Nos. 5,294,770 and 5,399,828 owned by Alza Corporation, each of which is incorporated in its entirety by reference herein. In accord with these inventions, multi-layer osmotic tablets are supplied in a manner that permits laser access to both the front and the back surface of the dosage form. A suitable color detector is used to determine which surface encompasses the dispensing end of the tablet and, then, a laser controller directs the laser to drill at least one delivery port in that end.
The above-described methods have been shown to be especially satisfactory for conventional tablet shapes where the dispensing end and the push end of the tablet coincide with the front and back surfaces of the tablet. Because these surfaces are relatively broad and flat, a color detector is able to accurately and rapidly determine the color and generate an appropriate signal to direct the laser. More recently, it has been discovered that capsule shaped osmotic tablets having the dispensing end at one narrow and rounded end of the capsule-shaped tablet and the push end is at the opposite narrow and rounded end of the capsule-shaped tablet are preferable to conventional tablet shapes for certain applications. Unfortunately, because the narrow and rounded ends of the capsule-shaped tablets scatter a significant portion of light directed thereon, the above-described methods for determining the formulation orientation of the dosage forms by detecting the color at the narrow and rounded ends corresponding to the dispensing end and push end of the tablet are not satisfactory.
Pharmaceutical manufacturing in general requires high speed, efficiency and accuracy and it is generally desirable to provide as many automated steps as possible. It would be an advance in the art to develop rapid and accurate automated color-detection methods and apparatus for determining the formulation orientation of multi-layer capsule-shaped osmotic dosage forms with respect to different internal formulation layers proximate to the opposite narrow and rounded ends of the tablets.